Association between blood lead levels and markers of calcium homeostasis: a systematic review and meta-analysis

Abstract

Chronic Pb exposure associated systemic illness are partly posited to involve calcium homeostasis. Present systematic review aims to comprehensively evaluate the association between chronic lead exposure and markers of calcium homeostasis. Observational studies documenting the changes in calcium homeostasis markers (i.e. serum calcium, parathyroid hormone, vitamin D & calcitonin) between occupationally Pb exposed group and control group were systematically searched from pubmed-Medline, Scopus, and Embase digital databases since inception to September 24, 2021. The protocol was earlier registered at PROSPERO (ID: CRD42020199503) and executed adhering to PRISMA 2020 guidelines. Mean differences of calcium homeostasis markers between the groups were analysed using random-effects model. Conventional I² statistics was employed to assess heterogeneity, while the risk for various biases were assessed using Newcastle Ottawa Scale. Sub-group, sensitivity and meta-regression analyses were performed where data permitted. Eleven studies including 837 Pb exposed and 739 controls were part of the present study. Pb exposed group exhibited higher mean blood lead level [i.e. 36.13 (with 95% CI 25.88-46.38) µg/dl] significantly lower serum calcium (i.e. - 0.72 mg/dl with 95% CI - 0.36 to - 1.07) and trend of higher parathyroid levels and lower vitamin D levels than controls. Heterogeneity was high (I² > 90%) among the studies. Considering the cardinal role of calcium in multiple biological functions, present observations emphasis the need for periodic evaluation of calcium levels and its markers among those with known cumulative Pb exposure.

Figure 1

PRISMA flow chart. Legends: PRISMA flow chart illustrating the number of records included and excluded at various screening and revieweing steps, leading to final list of records for data extraction and meta-analysis.

Figure 2

Forest plot for association between occupational Pb exposure and Blood lead levels. (Legends/footnotes): forest plot revealing the group mean differences of blood lead levels (BLL) in µg/dl between the occupationally Pb exposed workers and control participants (i.e. without obvious Pb exposure). The square and whisker (horizontal lines) represent respectively the mean difference and 95% confidence interval of individual studies. The length and width of the diamond indicate the pooled mean difference and 95% confidence interval derived from random-effect analysis.

Figure 3

Forest plot for association between occupational Pb exposure and blood calcium levels. (Legends/footnotes): forest plot revealing the group mean differences in serum calcium (A) and ionised calcium (B) levels in mg/dl between the occupationally Pb exposed workers and control participants. The square and whisker (horizontal lines) represent respectively the mean difference and 95% confidence interval of individual studies. The length and width of the diamond indicate respectively the pooled mean difference and 95% confidence interval derived from random-effect analysis.

Figure 4

Forest Plot for parathormone (A) and Vitamin D (B). (Legends/footnotes) Group differences in paratharmone (A) and vitamin D (B) between the occupationally Pb exposed and unexposed control workers. Forest plot for association between occupational Pb exposure and Paratharmone (A) and Vitamin D (B) levels. (Legends/footnotes): Forest plot revealing the group mean differences in parathormone in pg/dl (A) and vitamin D in ng/dl (B) between the occupationally Pb exposed workers and control participants. The square and whisker (horizontal line) represent respectively the mean difference and 95% confidence interval of individual studies. The length and width of the diamond indicate respectively the pooled mean difference and 95% confidence interval derived from random-effect analysis.